| Entity | inv (11)(p15q22)/ myelodysplasic syndrome (MDS) or acute non lymphocytic leukemia (ANLL) --> NUP98-DDX10 |
| Disease | therapy related MDS (t-MDS) and ANLL; de novo ANLL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' DDX10 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the acidic domain of DDX10 |
| | |
| Entity | t(1;11)(q23;p15.5) / t-MDS orANLL --> NUP98-PMX1 |
| Disease | One case of t-ANLL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' PMX1 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the homeodomain of PMX1 |
| | |
| Entity | t(2;11)(q31;p15)/treatment related leukaemia --> NUP98-HOXD13 |
| Disease | so far, only 1 case of treatment related myelodysplasia evolving towards M6 acute non lymphocytic leukaemia |
| Hybrid/Mutated Gene | 5' NUP98 - 3' HOXD13 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the HOXD13 homeodomain |
| | |
| Entity | t(4;11)(q21;p15.5)/ T- acute lymphoblastic leukemia (ALL) --> NUP98-RAP1GDS1 |
| Disease | 3 cases of adult T-ALL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' RAP1GDS1 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the entire coding region of RAP1GDS1. The product, rap1gds, has guanine nucleotide exchange factor activity. |
| | |
| Entity | t(5;11)(q35;p15.5)/ ANLL--> NUP98-NSD1 |
| Disease | ANLL. 5 cases reported to date. All were children or young adults (age range 3-18 years). Note that the t(5;11)(q35;p15.5) is not detectable by G-banding. Three cases were reported as cryptic t(5;11) associated with del(5q); a further two cases were identified in apparently normal karyotypes. |
| Hybrid/Mutated Gene | 5' NUP98 - 3' NSD1 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the conserved SET, SAC and PHD finger domains of the NSD1 gene. |
| | |
| Entity | t(7;11)(p15;p15) /ANLL --> NUP98-HOXA9 |
| Disease | M2-M4 ANLL mostly; occasionally: CML-like cases |
| Prognosis | mean survival: 15 mths |
| Cytogenetics | sole anomaly most often |
| Hybrid/Mutated Gene | 5' NUP98 - 3' HOXA9 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the HOXA9 homeobox |
| | |
| Entity | t(9;11)(p22;p15.5)/ANLL--> NUP98-LEDGF |
| Disease | One case of de novo ANLL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' LEDGF |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the COOH terminal of the LEDGF gene (encoding transcriptional activators p52 and p75) |
| | |
| Entity | t(11;12)(p15;q13)/treatment related leukemia (t-ANLL/MDS) |
| Disease | 1patient with t-MDS/ANLL |
| Hybrid/Mutated Gene | 5'; NUP98 - 3'; unknown |
| | |
| Entity | t(11;17)(p15.5;q21) t-MDS/ANLL |
| Disease | 1 patient with t-MDS/ANLL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' unknown |
| | |
| Entity | t(11;20)(p15.5;q11)/ANLL, t-MDS/ANLL--> NUP98-TOP1 |
| Disease | ANLL, t-MDS/ANLL |
| Hybrid/Mutated Gene | 5' NUP98 - 3' TOP1 |
| Abnormal Protein | fuses the GLFG repeat domains of NUP98 to the catalytic domain of TOP1 |
| | |
| Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. |
| Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy JD Jr |
| Nature genetics. 1996 ; 12 (2) : 154-158. |
| PMID 8563753 |
| |
| The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10. |
| Arai Y, Hosoda F, Kobayashi H, Arai K, Hayashi Y, Kamada N, Kaneko Y, Ohki M |
| Blood. 1997 ; 89 (11) : 3936-3944. |
| PMID 9166830 |
| |
| The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways. |
| Powers MA, Forbes DJ, Dahlberg JE, Lund E |
| The Journal of cell biology. 1997 ; 136 (2) : 241-250. |
| PMID 9015297 |
| |
| NUP98-HOXD13 gene fusion in therapy-related acute myelogenous leukemia. |
| Raza-Egilmez SZ, Jani-Sait SN, Grossi M, Higgins MJ, Shows TB, Aplan PD |
| Cancer research. 1998 ; 58 (19) : 4269-4273. |
| PMID 9766650 |
| |
| The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. |
| Ahuja HG, Felix CA, Aplan PD |
| Blood. 1999 ; 94 (9) : 3258-3261. |
| PMID 10556215 |
| |
| The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. |
| Hussey DJ, Nicola M, Moore S, Peters GB, Dobrovic A |
| Blood. 1999 ; 94 (6) : 2072-2079. |
| PMID 10477737 |
| |
| A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG) |
| Jaju RJ, Haas OA, Neat M, Harbott J, Saha V, Boultwood J, Brown JM, Pirc-Danoewinata H, Krings BW, Mˆºller U, Morris SW, Wainscoat JS, Kearney L |
| Blood. 1999 ; 94 (2) : 773-780. |
| PMID 10397745 |
| |
| A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG) |
| Jaju RJ, Haas OA, Neat M, Harbott J, Saha V, Boultwood J, Brown JM, Pirc-Danoewinata H, Krings BW, Mˆºller U, Morris SW, Wainscoat JS, Kearney L |
| Blood. 1999 ; 94 (2) : 773-780. |
| PMID 10397745 |
| |
| NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15). |
| Nakamura T, Yamazaki Y, Hatano Y, Miura I |
| Blood. 1999 ; 94 (2) : 741-747. |
| PMID 10397741 |
| |
| Potential role for DNA topoisomerase II poisons in the generation of t(11;20)(p15;q11) translocations. |
| Ahuja HG, Felix CA, Aplan PD |
| Genes, chromosomes & cancer. 2000 ; 29 (2) : 96-105. |
| PMID 10959088 |
| |
| t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF). |
| Ahuja HG, Hong J, Aplan PD, Tcheurekdjian L, Forman SJ, Slovak ML |
| Cancer research. 2000 ; 60 (22) : 6227-6229. |
| PMID 11103774 |
| |
| A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. |
| Jaju RJ, Fidler C, Haas OA, Strickson AJ, Watkins F, Clark K, Cross NC, Cheng JF, Aplan PD, Kearney L, Boultwood J, Wainscoat JS |
| Blood. 2001 ; 98 (4) : 1264-1267. |
| PMID 11493482 |
| |
| NUP98 gene fusions in hematologic malignancies. |
| Lam DH, Aplan PD |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (11) : 1689-1695. |
| PMID 11681408 |
| |
| A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay. |
| Brown J, Jawad M, Twigg SR, Saracoglu K, Sauerbrey A, Thomas AE, Eils R, Harbott J, Kearney L |
| Blood. 2002 ; 99 (7) : 2526-2531. |
| PMID 11895789 |
| |
